N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-4-(pyridin-4-ylsulfonyl)piperazin-2-yl)propan-2-yl)-5-methyl-N3,N3-dipropylisophthalamide | 1230559-20-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-4-(pyridin-4-ylsulfonyl)piperazin-2-yl)propan-2-yl)-5-methyl-N3,N3-dipropylisophthalamide
• 英文别名: 1-N-[(1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-[(2R)-4-pyridin-4-ylsulfonylpiperazin-2-yl]propan-2-yl]-5-methyl-3-N,3-N-dipropylbenzene-1,3-dicarboxamide
• CAS: 1230559-20-2
• 化学式: C₃₃H₄₁F₂N₅O₅S
• 分子量: 657.782
• InChiKey: MCXKQZCXENNNEH-YPKYBTACSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  tert-butyl (R)-2-((1S,2S)-3-(3,5-difluorophenyl)-2-(3-(dipropylcarbamoyl)-5-methylbenzamido)-1-hydroxypropyl)-4-(pyridin-4-ylsulfonyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-4-(pyridin-4-ylsulfonyl)piperazin-2-yl)propan-2-yl)-5-methyl-N3,N3-dipropylisophthalamide
  参考文献：
  名称：

  Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

  摘要：

  With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A beta(40) in transgenic mice with a single subcutaneous dose. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.050

文献信息

• Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization
  作者：Jared Cumming、Suresh Babu、Ying Huang、Carolyn Carrol、Xia Chen、Leonard Favreau、William Greenlee、Tao Guo、Matthew Kennedy、Reshma Kuvelkar、Thuy Le、Guoqing Li、Nansie McHugh、Peter Orth、Lynne Ozgur、Eric Parker、Kurt Saionz、Andrew Stamford、Corey Strickland、Dawit Tadesse、Johannes Voigt、Lili Zhang、Qi Zhang

  DOI：10.1016/j.bmcl.2010.03.050

  日期：2010.5

  With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A beta(40) in transgenic mice with a single subcutaneous dose. (C) 2010 Elsevier Ltd. All rights reserved.